Protein synthesis and the heart shock/stress response after ischemia.
It has been appreciated for many years that the recovery of brain protein synthesis activity following a transient ischemic insult lags considerably behind the normalization of brain energy metabolism. More recently, selective increases or decreases in the synthesis of specific proteins have been documented to occur during postischemic recirculation, the best characterized of such changes being the induction of proteins characteristic of the "heat shock" or "stress" response. This review will summarize these developments in the study of changes in gene expression following ischemia, with an emphasis on regional differences in the vulnerability of overall translational activity as well in the expression of stress proteins and their mRNAs. The neuronal localization of the 70 kDa heat shock protein, hsp70, after ischemia is contrasted with its largely glial and vascular induction following a hyperthermic stress. The lasting depression of protein synthesis and sustained expression of hsp70 mRNA in vulnerable hippocampal CA1 neurons appear to be mechanistically related and may constitute markers for cellular pathophysiology leading to neuronal cell loss. Elucidating the mechanisms responsible for cell-specific regulation of stress proteins and other gene products may eventually contribute to a more precise understanding of the evolution of brain injury at the molecular level following diverse insults.
Nowak
T S
TS
Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
D000818:Animals; D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013312:Stress, Physiological / Q000378:metabolism
D006360:Heat-Shock Proteins; D011506:Proteins; D012333:RNA, Messenger